Functional effects of drugs and toxins interacting with NaV1.4

Xinyi Zou; Zixuan Zhang; Hui Lu; Wei Zhao; Lanying Pan; Yuan Chen

doi:10.3389/fphar.2024.1378315

Functional effects of drugs and toxins interacting with Na_V1.4

Front Pharmacol. 2024 Apr 25:15:1378315. doi: 10.3389/fphar.2024.1378315. eCollection 2024.

Authors

Xinyi Zou^#¹, Zixuan Zhang^#¹, Hui Lu¹, Wei Zhao¹, Lanying Pan², Yuan Chen¹

Affiliations

¹ Zhejiang Provincial Key Laboratory of Resources Protection and Innovation of Traditional Chinese Medicine, College of Food and Health, Zhejiang Agriculture and Forestry University, Hangzhou, China.
² Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China.

^# Contributed equally.

Abstract

Na_V1.4 is a voltage-gated sodium channel subtype that is predominantly expressed in skeletal muscle cells. It is essential for producing action potentials and stimulating muscle contraction, and mutations in Na_V1.4 can cause various muscle disorders. The discovery of the cryo-EM structure of Na_V1.4 in complex with β1 has opened new possibilities for designing drugs and toxins that target Na_V1.4. In this review, we summarize the current understanding of channelopathies, the binding sites and functions of chemicals including medicine and toxins that interact with Na_V1.4. These substances could be considered novel candidate compounds or tools to develop more potent and selective drugs targeting Na_V1.4. Therefore, studying Na_V1.4 pharmacology is both theoretically and practically meaningful.

Keywords: Nav1.4; drug design; mexiletine; skeletal muscle; tetrodotoxin; voltage-gated channel.

Publication types

Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was supported by Zhejiang Provincial Natural Science Foundation of China under Grant No. LY20C040001 to LP and Grant No. LBY22H270002 to WZ; it was also supported by Scientific Research and Development Fund of Zhejiang Shuren University (2023R009) to LP.